Cryoanalgesia to treat phantom limb pain following a trans-femoral (above-knee) amputation: a randomized, sham-controlled pilot study

Background A previous clinical trial applied percutaneous cryoneurolysis to lower limb amputees with phantom pain. The primary outcome measure was negative, but a secondary analysis suggested that patients with a below-knee amputation (BKA) improved, while the opposite was true for above-knee amputations (AKA). We theorized two potential reasons for this difference: cryoneurolysis was inadequate for the larger sciatic nerve in the upper thigh for AKA versus the lower thigh for BKA; and BKA is innervated by only two nerves, both of which were treated while AKA involved two additional nerves left untreated. Methods Participants with an existing AKA and intractable phantom pain had four nerves treated with ultrasound-guided percutaneous cryoneurolysis in the upper thigh: sciatic, femoral, obturator, lateral femoral cutaneous. For the larger nerves, we used an argon-based machine capable of inducing temperatures as low as −100°C and producing a relatively large ice ball. The sciatic nerve was treated both on the anterior and posterior aspects (5.5 min each). Participants were randomized to receive active or sham treatment with the option to return 4–6 months later for a crossover treatment. Participants and assessors were masked to treatment group allocation. Percutaneously inserted thermocouples were used to measure tissue temperature. Statistical analysis was not performed due to the limited sample size of this pilot study. Results After 1-month, average phantom limb pain intensity (primary outcome) was 5.0 (5.0, 6.0) in patients given cryoneurolysis (n=11) vs 5.0 (4.8, 5.3) for sham (n=5). Patients’ Global Impression of Change and the Brief Pain Inventory (interference subscale) similarly suggested no improvement in either group after the initial post-treatment week. Tissue 3 mm from the cryoprobe required 2.5 min to reach −20°C and did not reach −40°C by the end of the freeze cycle. Conclusions We found no evidence that percutaneous cryoneurolysis of the four major nerves of the thigh with an argon-based machine improved lower extremity phantom pain 1 month following treatment. Due to the limited sample size and probable lack of therapeutically low temperatures across the entire sciatic nerve, these results should be viewed as preliminary and used to help guide future preclinical and clinical investigations. Trial registration number NCT06071715 .